The application of surface-enhanced Raman spectroscopy (SERS) in biological and biomedical detection schemes is feasible due to its excellent molecular specificity and high sensitivity as well as the ...capability of SERS to be performed in complex biological compositions. SERS-based investigation of cells, which are the basic structure and functional unit of organisms, represents the starting point of this review. It is demonstrated that SERS provides a deep understanding of living cells as well as their microenvironment which is needed to assess the development of diseases. The clinical relevance of SERS is proved by its application for the detection of cancer cells and tumour margins under
in vivo
conditions and examples for theranostic approaches are discussed. This review article provides a comprehensive overview of the recent progress within the last 3 years.
In this tutorial review, we summarize the recent progress in SERS-based biological and biomedical applications - from cells to clinics.
The Monkhorst-Pack scheme is a method to save time in the days of slow computers. It excludes umklapp phonons with significant consequences. Its widespread application to evaluate superconductivity ...arises from the desire to reduce phonon contributions to solve a historical difficulty of the BCS theory. An alternative method turns out to be more accurate in Pb and Pd.
The Monkhorst-Pack scheme is a method to save time in the days of slow computers. It excludes umklapp phonons and offers erroneous evaluations in superconducting Pb and Pd (curves). An alternative method leads to better results (silhouettes).
Superoxide dismutase 1 (Sod1) has been known for nearly half a century for catalysis of superoxide to hydrogen peroxide. Here we report a new Sod1 function in oxidative signalling: in response to ...elevated endogenous and exogenous reactive oxygen species (ROS), Sod1 rapidly relocates into the nucleus, which is important for maintaining genomic stability. Interestingly, H2O2 is sufficient to promote Sod1 nuclear localization, indicating that it is responding to general ROS rather than Sod1 substrate superoxide. ROS signalling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to promoters and regulates the expression of oxidative resistance and repair genes. Altogether, our study unravels an unorthodox function of Sod1 as a transcription factor and elucidates the regulatory mechanism for its localization.
The exhaustive body of literature published in the last four years on the development and application of systems based on surface-enhanced Raman spectroscopy (SERS) combined with microfluidic devices ...demonstrates that this research field is a current hot topic. This synergy, also referred to as lab-on-a-chip SERS (LoC-SERS) or nano/micro-optofluidics SERS, has opened the door for new opportunities where both techniques can profit. On the one hand, SERS measurements are considerably improved because the processes previously performed on a large scale in the laboratory and prone to human error can now be carried out in nanoliter volumes in an automatic and reproducible manner; on the other hand, microfluidic platforms need detection methods able to sense in small volumes and therefore, SERS is ideal for this task. The present review not only aims to provide the reader an overview of the recent developments and advancements in this field, but it also addresses the key aspects of fundamental SERS theory that influence the interpretation of SERS spectra, as well as the challenges brought about by the experimental conditions and chemometric data analysis.
The review provides an overview of the development in the field of surface-enhanced Raman spectroscopy combined with microfluidic platforms.
Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized in the liver, and its main function ...is to cleave von Willebrand factor (VWF) anchored on the endothelial surface, in circulation, and at the sites of vascular injury. Deficiency of plasma ADAMTS13 activity (<10%) resulting from mutations of the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or acquired (idiopathic) TTP. ADAMTS13 activity is usually normal or modestly reduced (>20%) in other forms of thrombotic microangiopathy secondary to hematopoietic progenitor cell transplantation, infection, and disseminated malignancy or in hemolytic uremic syndrome. Plasma infusion or exchange remains the initial treatment of choice to date, but novel therapeutics such as recombinant ADAMTS13 and gene therapy are under development. Moreover, ADAMTS13 deficiency has been shown to be a risk factor for the development of myocardial infarction, stroke, cerebral malaria, and preeclampsia.
Mergers of neutron stars are known to be associated with short γ-ray bursts
. If the neutron-star equation of state is sufficiently stiff (that is, the pressure increases sharply as the density ...increases), at least some such mergers will leave behind a supramassive or even a stable neutron star that spins rapidly with a strong magnetic field
(that is, a magnetar). Such a magnetar signature may have been observed in the form of the X-ray plateau that follows up to half of observed short γ-ray bursts
. However, it has been expected that some X-ray transients powered by binary neutron-star mergers may not be associated with a short γ-ray burst
. A fast X-ray transient (CDF-S XT1) was recently found to be associated with a faint host galaxy, the redshift of which is unknown
. Its X-ray and host-galaxy properties allow several possible explanations including a short γ-ray burst seen off-axis, a low-luminosity γ-ray burst at high redshift, or a tidal disruption event involving an intermediate-mass black hole and a white dwarf
. Here we report a second X-ray transient, CDF-S XT2, that is associated with a galaxy at redshift z = 0.738 (ref.
). The measured light curve is fully consistent with the X-ray transient being powered by a millisecond magnetar. More intriguingly, CDF-S XT2 lies in the outskirts of its star-forming host galaxy with a moderate offset from the galaxy centre, as short γ-ray bursts often do
. The estimated event-rate density of similar X-ray transients, when corrected to the local value, is consistent with the event-rate density of binary neutron-star mergers that is robustly inferred from the detection of the gravitational-wave event GW170817.
Targeted therapy of immune thrombotic thrombocytopenic purpura (iTTP) requires acurate and prompt diagnosis and differentiation from complement‐mediated hemolytic uremic syndrome and other causes of ...thrombotic microangiopathy. ADAMTS‐13 (A Disintegrin And Metalloprotease with ThromboSpondin‐1 Domain, member 13) evaluation (activity and inhibitors or anti‐ADAMTS‐13 IgG) is the key for diagnosis and further management of patients with suspected iTTP during acute episode and in clinical response or remission. Clinical trial results and real‐world data have demonstrated the efficacy and safety of the triple therapy consisting of therapeutic plasma exchange, caplacizumab, and immunosuppressives (e.g., corticosteroids and rituximab) for acute iTTP. Such a therapeutic strategy has significantly accelerated the normalization of platelet counts, decreased the length of stays in the intensive care unit and the hospital, but most importantly reduced the mortality rate. The present review highlights some of the important advancements for the diagnosis and management of iTTP and proposes triple therapy as the standard of care for acute iTTP today.
Amino acid (AA) is a potent mitogen that controls growth and metabolism. Here we describe the identification of Rab1 as a conserved regulator of AA signaling to mTORC1. AA stimulates Rab1A GTP ...binding and interaction with mTORC1 and Rheb-mTORC1 interaction in the Golgi. Rab1A overexpression promotes mTORC1 signaling and oncogenic growth in an AA- and mTORC1-dependent manner. Conversely, Rab1A knockdown selectively attenuates oncogenic growth of Rab1-overexpressing cancer cells. Moreover, Rab1A is overexpressed in colorectal cancer (CRC), which is correlated with elevated mTORC1 signaling, tumor invasion, progression, and poor prognosis. Our results demonstrate that Rab1 is an mTORC1 activator and an oncogene and that hyperactive AA signaling through Rab1A overexpression drives oncogenesis and renders cancer cells prone to mTORC1-targeted therapy.
•Rab1A mediates amino acid signaling to activate mTORC1 independently of Rag•Rab1A regulates mTORC1-Rheb interaction on the Golgi apparatus•Rab1A is an oncogene that is frequently overexpressed in human cancer•Hyperactive amino acid signaling is a common driver for cancer
Thomas et al. show that Rab1 is a regulator of amino acid (AA) signaling to mTORC1, Rab1A overexpression promotes AA- and mTORC1-dependent oncogenic growth, and Rab1A overexpression in colorectal cancer correlates with increased mTORC1 activity, tumor progression, and poor patient prognosis.
Immune-mediated thrombotic thrombocytopenic purpura is caused by autoantibodies against ADAMTS-13, a plasma enzyme that cleaves von Willebrand factor. However, the mechanism resulting in severe ...deficiency of plasma ADAMTS-13 activity remains controversial.
To determine the mechanism of autoantibody-mediated severe deficiency of plasma ADAMTS13 activity in immune-mediated thrombotic thrombocytopenic purpura.
Fluorescence resonance energy transfer-VWF73 was used to determine plasma ADAMTS-13 activity. Enzyme-linked immunosorbent assay (ELISA) was used to determine anti–ADAMTS-13 immunoglobulin G. ELISA and capillary electrophoresis–based Western blotting were employed to assess plasma ADAMTS-13 antigen.
We showed that plasma ADAMTS-13 antigen levels varied substantially in the samples collected on admission despite all showing plasma ADAMTS-13 activity of <10 IU/dL (or <10% of normal level) using either ELISA or Western blotting. More severe deficiency of plasma ADAMTS-13 antigen (<10%) was detected in admission samples by ELISA than by capillary Western blotting. There was a significant but moderate correlation between plasma ADAMTS-13 activity and ADAMTS-13 antigen by either assay method, suggesting that severe deficiency of plasma ADAMTS-13 activity is not entirely associated with low levels of ADAMTS-13 antigen.
We conclude that severe deficiency of plasma ADAMTS-13 activity primarily resulted from antibody-mediated inhibition, but the accelerated clearance of plasma ADAMTS-13 antigen via immune complexes may also contribute significantly to severe deficiency of plasma ADAMTS-13 activity in a subset of patients with acute immune-mediated thrombotic thrombocytopenic purpura.
In recent years, thermoelectric (TE) devices have emerged as promising alternative environmental friendly applications for heat pumps and power generators since the environmental issues such as the ...global warming and the limitations of energy resources gradually drew worldwide attentions. Due to the green feature and distinct advantages, the thermoelectric technology have been applied to different areas in an effort of designing simple, compact and environmental friendly systems. The applied areas are extended from the earliest application on kerosene lamp to aerospace applications, transportation tools, industrial utilities, medical services, electronic devices and temperature detecting and measuring facilities. The application potentials of TE in directly conversing thermal energy into electrical power have been identified, especially for where the cost of thermal energy input need not to be considered, such as waste heat utilization, in the light of the present low efficiency of thermoelectric conversion. The capability of TE in producing thermal energy (in terms of cooling or heating) with the use of electrical power is also well identified. This paper reviews the status of the material development and thermoelectric applications in different areas and discusses the difficulties in terms of the commercialisations of advanced materials. Other than this, the main purpose of this paper is to present the great potential of achieving both environmental and economic benefits by exclusively utilizing thermoelectric applications in different areas. It also comes to the conclusion that the thermoelectric applications with the current conversion efficiency are economically and technically practical for micro/small applications. However, it would be transformed to a more significant green energy solution for improving the current environment and energy issues by using medium/large scale thermoelectric applications when the thermoelectric materials with a figure-of-merit over 2 come into commercial practice.